Based on the mechanism of action of gamma-aminobutyric acid transaminase, specific irreversible inactivators have been designed and some synthesized. Preliminary studies show that at least one of these compounds an irreversible inactivator of the enzyme in vitro. In this proposal mechanisms by which these compounds would inactivate the purified enzyme are suggested. Experiments will be carried out to investigate these reactions and information obtained can be used for further design of inactivators. Certain known inhibitors of GABA transaminase actually may be irreversible inactivators and this will also be investigated. The active-site residues which are labeled by the different inactivators will be determined.